Alzheimer disease (AD) remains a clinico-pathologic entity. A definitive diagnosis of AD requires the identification of senile plaques (SP) and neurofibrillary tangles (NFT) in appropriate density in hippocampus and neocortex in a patients who was clinically demented. In addition, no completely suitable animal model exists yet, so AD researchers must utilize human tissue to characterize the alterations in the brain associated with AD. The major responsibilities of this Core are to perform the neuropathologic studies necessary to document the diagnosis of AD or other pathologic entities in all human brain specimens used in research studies proposed by investigators within and outside of the Alzheimer Disease Center (ADC), and to provide clinico-pathologic correlation for ADC Clinical Core patients. Therefore, in Specific Aim , we will maintain a human brain bank wherein we propose to 1) correct, prepare, evaluate, catalog, store, and distribute well-characterized postmortem and quantitative diagnostic information to physicians, families, and researchers; 3) work with the Clinical Core to acquire relevant medical records regard deceased subjects' illnesses, including detailed perimortem information (circumstances surrounding death), for clinic0-pathologic correlation; and 4) regularly update the central ADC and Alzheimer Disease Data Coordinating Center (ADDCC) databases with diagnostic and other related information on autopsied and biopsied and biopsied subjects. In addition, to Specific Aim 3, in response to criticism by the reviewers of the original ADC application, and to enhance the neuropathologic characterization of brain tissue accessioned through this core, we will also focus on providing more extensive quantitative neuropathologic evaluations of correlation with clinical and other research data. The specific analyses to be performed will include 1) quantification of synapse density (by measuring concentration of synaptophysin) and concentration of abnormal proteins (e.g., tau) in postmortem neocortex using enzyme-linked immunosorbent assays (ELISA); and 2) quantification of neocortical neuritic dystrophy in sections immunostained for tau and -synuclein using image analysis.